Certain clay minerals have been shown to inhibit growth of some bacterial pathogens. Using modern methods to analyze the nano-scale chemical and structural properties of these minerals we seek to identify the bactericidal mechanism, thus allowing us to design new antibacterial agents. This alternative therapeutic treatment may be especially valuable in treatment of mycobacterial diseases of the skin such as Buruli ulcer. Buruli ulcer is the third most common mycobacterial disease of immunocompetent humans with endemic rates in much of central and western Africa. In some West African communities, it has replaced tuberculosis and leprosy as the most prevalent mycobacterial disease. Although the global burden of Buruli ulcer is unknown, the disease has also been reported in the Americas, Asia, Australia, and Papua New Guinea and is most common in children. To address the rising incidence, the World Health Organization (WHO) has declared Buruli ulcer an emerging public health threat. The characteristic necrotic ulcers lead to very extensive skin loss, damage to nerves, blood vessels, and appendages, and deformity and disability, particularly in children. Despite the severity of the illness and the disfiguring ulceration, there is no known therapeutic treatment available for Buruli ulcer. Currently, the only accepted treatment of Mycobacterium ulcerans infection is surgical excision of the necrotic lesion and subsequent skin grafting or amputation. The predilection of the disease for underprivileged populations in poor rural communities makes the cost and complications of these complex surgical procedures an unlikely treatment option. Considering the lack of therapeutics for treating this debilitating disease, we intend to investigate the chemical properties of clay minerals that are responsible for eliciting antibacterial activity. Although potentiation of innate immunity may be involved, we will first determine direct effects on the microbes using French clays that have undergone rigorous product quality evaluation. We propose to (1) assess the broad-spectrum antibacterial effects of the clay mineral especially with regard to mycobacteria, (2) determine if the crystal structure and surface properties of the clay mineral are responsible for its antibacterial effects, (3) identify the specific, toxic components of the clay mineral responsible for antibacterial activity, and (4) monitor chemical exchange between the mineral and bacteria by isotopic labeling, leading to an examination of mechanisms of clay:mycobacterial interactions.